Annotating cancer variants and anti-cancer therapeutics in Reactome

Marija Milacic, Robin Haw, Karen Rothfels, Guanming Wu, David Croft, Henning Hermjakob, Peter D'Eustachio, Lincoln Stein

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of "cancer" pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)1180-1211
Number of pages32
JournalCancers
Volume4
Issue number4
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • Cancer annotation
  • EGFR signaling
  • Network visualization
  • Pathway database
  • Pathway visualization

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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